Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients. METHODS: We measured SP-resistance allele frequencies in Malawian women participating in a trial comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped polymerase chain reaction-detected parasites using deep sequencing of SP-resistance alleles. RESULTS: Among 125 placental infections, A581G-bearing parasites were associated with reduced birth weight (mean difference [MD], 252 g; 95% confidence interval [CI], 46-457; P = .017). Relative to ISTp, IPTp-SP was associated with higher birth weights in women with wild-type parasites (MD, 116 g; 95% CI, -40 to 272; P = .142) and lower birth weights in women with A581G-bearing parasites (MD, 192 g; 95% CI, -264 to 648; P = .385) (Pinteraction = .033). Similar associations were noted on gestational age (Pinteraction = .075). Amongst only IPTp-SP recipients, relative to women who last received SP > 4 weeks before delivery, recent SP receipt was associated with lower birth weight in women with wild-type parasites (MD, 118 g; 95% CI, -376 to 139; P = .361) and higher birth weight in women with A581G-bearing parasites (MD, 783 g; 95% CI, -20 to 1586; P = .054) (Pinteraction = .005). CONCLUSIONS: The effectiveness in birth weight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP. ISRCTN REGISTRY: www.isrctn.com/ISRCTN69800930.

Full Text

Duke Authors

Cited Authors

  • Taylor, SM; Levitt, B; Freedman, B; Madanitsa, M; Thwai, K-L; Kalilani-Phiri, L; Khairallah, C; Mwapasa, V; Ter Kuile, FO; Meshnick, SR

Published Date

  • July 23, 2020

Published In

Volume / Issue

  • 222 / 4

Start / End Page

  • 661 - 669

PubMed ID

  • 32221555

Pubmed Central ID

  • PMC7377291

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiaa145

Language

  • eng

Conference Location

  • United States